Project Summary The overarching goal of this proposal is to establish and follow a cohort of ethnically diverse pregnant women and their offspring in order to longitudinally explore the hypothesis that fetal over-nutrition is associated with obesity, metabolic and cardio- vascular abnormalities in offspring. As part of the current application, we propose to test the hypothesis that programming of neonatal adiposity is driven by maternal obesity per se, in the absence of frank gestational diabetes. To determine whether there are associations between specific maternal factors and neonatal outcomes we will examine the effects of maternal obesity, diet and weight gain during pregnancy, together with specific potential mediators measured prospectively throughout pregnancy (maternal fuels, markers of insulin-resistance and inflammation). These are factors that can be targeted by future interventions. We propose to enroll a total of 1,920 pregnant women before 15 weeks of gestation and follow them prospectively through delivery in order to explore the relationships between maternal body size and behaviors during pregnancy [pre-pregnant BMI, weight gain, diet], intra-partum fuels (glucose, lipids, FFA), markers of inflammation (IL-6, TNF-) and insulin resistance (HOMA-IR)], and infant body size (birth weight for gestational age), fatness (determined by air displacement plethysmography) and fat deposition (skinfolds). All women will have two fasting in- person visits, in early pregnancy (15-16 weeks of gestation, IPV1) and mid pregnancy (24-28 weeks of gestation, IPV2). This well characterized cohort of pregnant women will not only permit us to test important hypotheses related to programming of neonatal fatness (Aims 1 and 2), but will also be informative for the planned follow-up of the cohort of offspring assembled. To explore the relationships between maternal factors and infant metabolic markers, a random sample (N=300) of mother/infant pairs, enriched in women with GDM, will be selected to undergo a neonatal fasting blood draw protocol. Biomarkers traditionally associated with an increased risk of future cardiovascular disease, such as glucose, lipids (triglyceride, total and HDL-cholesterol, FFA), markers of insulin resistance (HOMA-IR) and insulin secretion, and markers of inflammation (TNF-, leptin) will be explored in these newborns (Aim 3).